Association of triglyceride-glucose index with adverse cardiovascular events in patients with established coronary artery disease according to different inflammatory status.

BACKGROUND AND AIMS: This study aimed to investigate the association of the triglyceride-glucose (TyG) index, a simple-but-reliable indicator of insulin resistance, with risk of cardiovascular (CV) events in coronary artery disease (CAD) patients with different inflammation status. METHODS AND RESULTS: We consecutively recruited 20,518 patients with angiograph-proven-CAD from 2017 to 2018 at Fuwai Hospital. Patients were categorized according to baseline TyG index tertiles (T) (tertile 1: ≤8.624; T2: 8.624-9.902 and T3: >9.902) and further assigned into 6 groups by high-sensitivity C-reactive protein (hsCRP) medians. The primary endpoint was CV events including CV death, nonfatal myocardial infarction and nonfatal stroke. During the 3.1-year-follow-up, 618 (3.0%) CV events were recorded. Overall, patients with high TyG index levels (T2 or T3) showed significantly increased risk of CV events (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.01-1.53; HR: 1.33; 95%CI: 1.05-1.68, respectively) compared with those with lowest Tyg index (T1) after adjusting for confounding factors. Upon stratification by hsCRP levels, elevated TyG index was associated with increased risk of CV events only in patients with hsCRP levels > median (per-1-unit-increase HR: 1.39; 95%CI: 1.11-1.74), rather than in those with hsCRP levels ≤ median. Furthermore, adding the TyG index to the predicting model led to a significant improvement in patients with hsCRP > median rather than in those with hsCRP ≤ median. CONCLUSIONS: We firstly found that elevated TyG index levels were associated with increased risk of CV events in CAD patients, especially in those with increased inflammatory status, suggesting that it could help in risk stratification and prognosis in this population.

The Neutrophil to Lymphocyte Ratio Modifies Lipoprotein (a)-Related Poor Prognosis in Patients After Percutaneous Coronary Intervention.

Lipoprotein (a) [Lp(a)] could contribute to coronary artery disease (CAD) through proinflammatory effects. The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker. We consecutively enrolled 7,922 CAD patients to investigate the synergistic association of Lp(a) and NLR with prognosis in patients undergoing percutaneous coronary intervention (PCI). NLR was calculated as the neutrophil count divided by the lymphocyte count. Cutoff for NLR was a median of 2.07. The threshold value was set at 30 mg/dL for Lp(a). The primary endpoint was major adverse cardiac events (MACEs), including all-cause mortality and myocardial infarction. During 2 years follow-up, 111 (1.40%) MACEs occurred. Lp(a) > 30 mg/dL was associated with an increased MACE risk in participants with NLR ≥2.07 [adjusted hazard ratio (HR), 1.84; 95% CI, 1.12-3.03], but not in participants with NLR <2.07 (adjusted HR, 0.74; 95% CI, 0.38-1.45) (Pinteraction = 0.021). Subgroup analysis demonstrated that the synergistic association of Lp(a) and NLR with prognosis was more pronounced in female patients (Pinteraction = 0.028). This study suggested that combining Lp(a) and NLR may be useful for risk stratification in CAD population.

Association of platelet-to-lymphocyte ratio levels with the risk of cardiac adverse events in people with type 2 diabetes undergoing percutaneous coronary intervention: A large-scale prospective cohort study.

BACKGROUND: The platelet-to-lymphocyte ratio (PLR), a promising inflammatory biomarker, contributes to the development of atherosclerosis and type 2 diabetes (T2D). Therefore, this study aimed to elucidate the importance of PLR in predicting adverse events in people undergoing percutaneous coronary intervention (PCI) with T2D. METHODS: We consecutively enrolled 8831 people who underwent PCI and divided them into four groups according to PLR and glycemic metabolic status (PLR-Low/High without T2D, PLR-Low/High with T2D). The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and stent thrombosis. A multivariate Cox regression analysis was performed to determine this association. RESULTS: During the 2.4-year follow-up, 663 (7.5%) MACCE and 75 (0.85%) stent thromboses were recorded. The risk of MACCE (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.10-1.53, P = 0.002) and stent thrombosis (HR: 2.32, 95% CI: 1.38-3.90, P = 0.002) was significantly higher in people with high PLR levels than in those with low PLR. Among people with T2D, the PLR-High group showed a significantly higher risk of MACCE (HR: 1.59, 95% CI: 1.21-2.09, P = 0.001) and stent thrombosis (HR: 3.15, 95% CI: 1.32-7.52, P = 0.010). However, these associations were not significant in people without T2D. CONCLUSIONS: PLR has been originally documented as a significant predictor of poor prognosis and a high incidence of stent thrombosis in people undergoing PCI, especially in those with T2D.

Triglyceride-glucose index as a suitable non-insulin-based insulin resistance marker to predict cardiovascular events in patients undergoing complex coronary artery intervention: a large-scale cohort study.

BACKGROUND: Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI. METHODS: This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke. RESULTS: During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13-1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96-1.45) or METS-IR (HR, 1.00; 95%CI 0.98-1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model. CONCLUSIONS: The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

Glycemic control and cardiovascular outcomes in patients with diabetes and coronary artery disease according to triglyceride-glucose index: a large-scale cohort study.

BACKGROUND: The role of triglyceride-glucose (TyG) index, an insulin resistance indicator, in glycemic management for diabetic patients with coronary artery disease (CAD) was still unknown. Therefore, we aimed to explore the association between glycemic control and cardiovascular (CV) outcomes in patients with diabetes and CAD according to different TyG index levels. METHODS: A total of 9996 diabetic patients with angiograph-proven CAD were consecutively recruited from 2017 to 2018 at Fuwai Hospital. Patients were assigned into 3 groups according to TyG index tertiles (T) (T1: <8.895; T2: 8.895-9.400; T3: ≥9.400). According to American Diabetes Association guidelines, controlled glycemia was defined as targeting glycosylated hemoglobin Alc (HbA1c) < 7%. The primary endpoint was CV events including CV death, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median 3-year follow-up, 381 (3.8%) CV events occurred. Overall, high TyG index (T3) was associated with increased risk of CV events (hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.02-1.94) compared with the lowest TyG index (T1) after multivariable adjustment. Upon stratification by the TyG index, in fully adjusted models, controlled glycemia was associated with reduced risk of CV events in the high TyG index (T3) subgroup (HR: 0.64; 95%CI: 0.42-0.96) but not in the low (T1; HR: 0.79; 95%CI: 0.53-1.16) and moderate (T2; HR: 0.84; 95%CI: 0.56-1.25) TyG index subgroups. CONCLUSIONS: Controlled glycemia was associated with improved CV outcomes in patients with diabetes and established CAD, especially in those with high TyG index levels. Our study, for the first time, provided valuable information that TyG index could help making risk stratification on the glycemic management in diabetic patients with CAD.

High absolute neutrophil count with type 2 diabetes is associated with adverse outcome in patients with coronary artery disease: A large-scale cohort study.

Background: Inflammatory processes crucially modulate the development, progression, and outcomes of coronary artery disease (CAD). Since hyperglycemia could alter inflammatory responses, this study aimed to investigate the effect of ANC, a novel and rapidly available inflammatory biomarker, on the prognosis of patients undergoing PCI with or without type 2 diabetes (T2D). Methods: A total of 7,826 patients with CAD hospitalized for PCI at Fuwai Hospital were consecutively recruited. According to the median ANC value, patients were stratified as having high ANC (ANC-H) or low ANC (ANC-L) and were further classified into four groups by T2D. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause mortality, myocardial infarction, stroke, and target vessel revascularization. Results: During a median follow-up of 2.4 years, 509 (6.5%) MACCEs were documented. Diabetic patients with increased ANC were at significantly higher risk of MACCEs (aHR, 1.55; 95% CI, 1.21-1.99; P = 0.001) compared to those in the ANC-L/non-T2D group (P for interaction between T2D and ANC categories = 0.044). Meanwhile, multivariable regression analysis demonstrated the highest MACCE risk in diabetic patients with a higher level of ANC than others (P for trend <0.001). Conclusion: This study suggests that stratification of patients with elevated ANC and T2D could provide prognostic information for CAD patients undergoing PCI.

HbA1c-based rather than fasting plasma glucose-based definitions of prediabetes identifies high-risk patients with angiographic coronary intermediate lesions: a prospective cohort study.

BACKGROUND: Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions. METHODS: A total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk. RESULTS: The proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143-2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005-2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden's index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients' outcome. CONCLUSIONS: In this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.

Clinicopathological characteristics and prognosis of resectable lung adenosquamous carcinoma: a population-based study of the SEER database.

OBJECTIVE: Adenosquamous carcinoma is a rare subtype of non-small cell lung cancer characterized by aggressive behavior, with combination of adenocarcinoma and squamous cell carcinoma components. The clinicopathological characteristics and prognosis of resectable adenosquamous carcinoma are incompletely understood and this study aimed to depict those in a large population. METHODS: A total of 805 adenosquamous carcinoma, 7875 squamous cell carcinoma and 23 957 adenocarcinoma patients who underwent lobectomy or sublobectomy were queried from the Surveillance, Epidemiology, and End Results database (2010-17). Clinicopathological characteristics of adenosquamous carcinoma patients were compared with those of squamous cell carcinoma and adenocarcinoma patients. Prognostic factors were identified by univariable and multivariable Cox regression analyses. Propensity score matching was applied to reduce confounding effects. RESULTS: Adenosquamous carcinoma was associated with higher pleural invasion incidence and poorer differentiation compared with squamous cell carcinoma or adenocarcinoma (P values < 0.001). The independent risk factors of cancer-specific survival of adenosquamous carcinoma patients were increasing age, male sex, invading through visceral pleura, poor differentiation and higher stage. Stage IB adenosquamous carcinoma patients whose tumor invaded through visceral pleura had significantly worse survival than those not (P = 0.003). Adenosquamous carcinoma patients had worse survival compared with squamous cell carcinoma (5-year-survival: 64.55 vs. 69.09%, P = 0.003) and adenocarcinoma (5-year-survival: 64.55 vs. 76.79%, P < 0.001) patients before match. And this difference persisted after match. CONCLUSIONS: Resectable adenosquamous carcinoma patients had higher pleural invasion incidence, poorer differentiation and worse survival compared with squamous cell carcinoma and adenocarcinoma patients. Visceral pleural invasion status and differentiation grade were vital prognostic factors of adenosquamous carcinoma patients on the basis of stage.

Pulmonary sclerosing pneumocytoma: clinical features and prognosis.

BACKGROUND: Pulmonary sclerosing pneumocytoma is a kind of rare benign pulmonary tumor with potential malignancy. The clinical features, risk factors for prognosis, and optimal treatment have not been identified yet. This study aimed to investigate the clinical features and prognosis of pulmonary sclerosing pneumocytoma. METHODS: We retrospectively performed a review of pulmonary sclerosing pneumocytoma patients in West China Hospital from 2009 to 2019. The basic characteristics, treatment regimens, operation detail, postoperative variables, and follow-up time were recorded for each case. Differences in features between patients undergoing lobectomy and segmentectomy were compared. We also performed a case review and summarized reported clinical features in former studies. RESULTS: Altogether 61 pulmonary sclerosing pneumocytoma patients were retrospectively reviewed. Fifty-six patients were female and 5 were male. The patients' median age was 51 (23-73). Seven (11.48%) patients had smoking history. Twenty tumors were located in the right lung [upper lobe (n = 7), middle (n = 2), and lower (n = 11)] and 41 in the left [upper (n = 12) and lower (n = 29)]. The median tumor size was 2 (0.9-7) cm. Thirty-six (59.02%) patients underwent sublobectomy (segmentectomy or wedge resection) whereas 25 (40.98%) underwent lobectomy. All patients recovered uneventfully, and no perioperative mortality was identified. Sublobectomy showed a trend towards reduced chest tube duration and shorter postoperative hospital stays compared with lobectomy. CONCLUSIONS: The findings showed good prognosis of pulmonary sclerosing pneumocytoma and proved its benign characteristics. Sublobectomy showed advanced efficacy regarding chest tube duration and postoperative hospital stay compared with lobectomy.

A new basic thoracoscopic surgical skill training and assessment system using automatic scoring techniques.

PURPOSE: We report a new thoracoscopic surgical skill training and assessment system with automatic scoring techniques, the Huaxi Intelligent Thoracoscopic Skill Training and Assessment (HITSTA) system. We also evaluated the discriminative ability of this system compared to our conventional scoring method at our institution. METHODS: We retrospectively collected training data of thoracic board-certified thoracic surgeons at West China Hospital, Sichuan University from January 1, 2018 to January 1, 2019. Surgeons were assessed by HITSTA system and human examiners simultaneously. Total scores were summed from 3 tasks (grasping with delivery, pattern cutting, and suture with knot). Bland-Altman analysis was used to test agreement of scores made by HITSTA system (automatic scoring) and human examiners (manual scoring). Differentiation ability was also compared between the two scoring methods. RESULTS: Thirty-nine surgeons were recruited. Scores made by HITSTA system and human examiners were not consistent. For suture with knot, automatic scoring method could detect the score differences between different training status (trained: 26.92 ± 12.04, untrained: 19.85 ± 11.12; p = 0.026) and training duration (< 10 h: 20.67 ± 15.23, ≥ 10 h: 31.92 ± 5.56; p = 0.003). For total scores, automatic scoring approach could discriminate between different training status (trained: 71.90 ± 12.63; untrained: 61.41 ± 13.87; p = 0.016) and training duration (< 10 h: 65.23 ± 15.31; ≥ 10 h 77.23 ± 6.94; p = 0.046). CONCLUSION: HITSTA system could discriminate the different levels of thoracoscopic surgical skills better than the traditional manual scoring method. Larger prospective studies are warranted to validate the differentiation ability of HITSTA system.

Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti-tuberculosis drug-induced hepatotoxicity: A prospective study.

BACKGROUND: The role of collagen type XVIII alpha 1 chain (COL18A1) in anti-tuberculosis drug-induced hepatotoxicity (ATDH) has not been reported. This study aimed to explore the association between of COL18A1 variants and ATDH susceptibility. METHODS: A total of 746 patients were enrolled in our study from December 2016 to April 2018, and all subjects in the study signed an informed consent form. The custom-by-design 2x48-Plex SNPscanTM kit was used to genotype all selected 11 SNPs. Categorical variables were compared by chi-square (χ2 ) or Fisher's exact test, while continuous variables were compared by Mann-Whitney's U test. Plink was utilized to analyze allelic and genotypic frequencies, and genetic models. Multivariate logistic regression analyses were used to adjust potential factors. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were also calculated. RESULTS: Among patients with successfully genotyping, there were 114 cases and 612 controls. The mutant A allele of rs12483377 conferred the decreased risk of ATDH (OR = 0.13, 95%CI: 0.02-0.98, P = 0.020), and this significance still existed after adjusting age and gender (P = 0.024). The mutant homozygote AA genotype of rs12483377 was associated with decreased total protein levels (P = 0.018). CONCLUSION: Our study first revealed that the A allele of COL18A1 rs12483377 was associated with the decreased risk of ATDH in the Western Chinese Han population, providing new perspective for the molecular prediction, precise diagnosis, and individual treatment of ATDH.

Does metformin improve the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor treatment for patients with advanced non-small-cell lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether metformin improved the efficacy of standard epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment for patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer. A total of 99 papers were found using the reported search, of which 4 represented the best evidence to answer this clinical question. The authors, journal, publication date, country, study type, treatment regimen, relevant outcomes and results of these papers are tabulated. We concluded that the addition of metformin to EGFR-TKI might improve the survival of patients with EGFR-mutated non-small-cell lung cancer and diabetes mellitus type 2. However, for non-diabetic non-small-cell lung cancer patients with EGFR mutation, the efficiency of additional metformin in EGFR-TKI treatment remains unclear because of the conflicting results of only 2 available studies.

The clinicopathological features and prognosis of primary pulmonary lymphoepithelioma-like carcinoma: A systematic review and meta-analysis.

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) was a sparse subtype of unclassified lung cancer. The clinicopathologic features, prognostic factors and multimodality treatment regimens of LELC remain inconclusive. We conducted this systematic review and meta-analysis to address this deficit in current knowledge. METHODS: We searched PubMed, Embase, and Web of Science to filtrate studies investigating on clinical features and prognostic factors of LELC up to Sep 9th, 2020. Fixed and random effect models were generated to present the incorporated hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI). The quality and heterogeneity of the included studies were also evaluated carefully. RESULTS: This systematic review and meta-analysis included 13 retrospective studies with a total of 1294 patients. The incidence of programmed cell death-ligand 1 (PD-L1) expression in PPLELC varied from 63.3% to 75.8%. Positive PD-L1 expression was more likely to be found in patients under 60 years old (OR = 2.16, 95%CI: 1.19-3.89, P = 0.01) and was associated with worse disease-free survival (DFS) compared with negative PD-L1 expression (HR = 2.99, 95%CI: 1.23-7.28, P = 0.02). The pooled results showed that stage was the prognostic factor for both overall survival (OS) and DFS. Moreover, a significantly better outcome of PPLELC was observed in men (HR = 0.56, 95%CI: 0.33-0.95, P = 0.03) and patients who received radiation (HR = 0.46, 95%CI: 0.22-0.96, P = 0.04). CONCLUSION: PD-L1 expression was high in PPLELC patients. It was significantly associated with age under 60 and the unfavorable DFS. Stage and gender could be the prognostic factor for OS. Radiation could be the effective therapy for PPLELC.

Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the prognostic value of lymph node ratio in non-small-cell lung cancer. METHODS: We searched systematically for eligible studies in PubMed, Web of Science, Medline (via Ovid) and Cochrane library through 6 November 2018. The primary outcome was overall survival. Disease-free survival and cancer-specific survival were considered as secondary outcomes. Hazard ratio with corresponding 95% confidence interval were pooled. Quality assessment of included studies was conducted. Subgroup analyses were performed based on N descriptors, types of tumor resection, types of lymphadenectomy and study areas. Sensitivity analysis and evaluation of publication bias were also performed. RESULTS: Altogether, 20 cohorts enrolling 76 929 patients were included. Mean Newcastle-Ottawa Scale was 7.65 ± 0.59, indicating the studies' quality was high. The overall result showed non-small-cell lung cancer patients with lower lymph node ratio was associated with better overall survival (HR: 1.946; 95% CI: 1.746-2.169; P < 0.001), disease-free survival (HR: 2.058; 95% CI: 1.717-2.467; P < 0.001) and cancer-specific survival (HR: 2.149; 95% CI: 1.864-2.477; P < 0.001). Subgroup analysis prompted types of lymphadenectomy and the station of positive lymph node have an important effect on the prognosis. No significant discovery was found in sensitivity analysis. CONCLUSION: Patients with lower lymph node ratio was associated with better survival, indicating that lymph node ratio may be a promising prognostic predictor in non-small-cell lung cancer. The type of lymphadenectomy, an adequate examined number and the removed stations should be considered for more accurate prognosis assessment.